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Table 2 Protein restriction results

From: Dietary restriction during the treatment of cancer: results of a systematic scoping review

Reference (author, year) Design Population (No. of participants, age, site/lesion type) Intervention (DR intervention, corresponding cancer treatment) Feasibility Tolerance Treatment effect
Eitan, 2017, USA [33] RCT 38 (19 IG, 19 CG)
Mean age 59.26 ± 7.5y
Prostate cancer
Protein restricted diet (0.8 g protein kg − 1 lean body mass)
Awaiting surgery (43 ± 11 days on diet)
NR NR ↔ EV size in either arm
↑ Levels of EV-associated LeR
↑ Y/S IRS1 ratio in neuronal-enriched EVs in IG vs CG
↓Body weight (kg) (− 2.62 ± 2.18 p = < 0.0001), FM (kg) (− 1.37 ± 1.55 p = 0.001), and BMI (− 0.76 ± 0.75 p = < 0.0001) in IG
Durando, 2008, France [34] Phase 1 clinical trial with single allocation 10
Median 68y (range 35-76y)
9 metastatic melanoma, 1 recurrent glioma
MET-free diet ranging from 1 to 4 days over 4 cycles of cystemustine chemotherapy Ppts consumed 72.4% ± 31.5% of the MET-free diet administered ↔ BMI, plasma albumin or NRI ↓MET conc., optimal depletion obtained on day 1 (− 40.7 ± 36.9% p < 0.05)
Nitrogen balance (g/24 h) stable and negative during MET-free diet (− 2.24 ± 3.16)
↓Daily 3MH:creatinin ratio from 29.9 ± 14.9 × 10–3 at D0 to 15.9 ± 4.9 × 10–3 at D4 (p < 0.05)
Grade 3 thrombocytopenia (33%), neutropenia (33%) and leucopenia (20%)
Durando, 2010, France [35] Feasibility study with single arm assignment 11
Median age 70y (range 48-78y)
Metastatic colorectal cancer
MET-free diet for 3 days over 3 cycles of FOLFOX chemotherapy Patients consumed 92.5% ± 21.8% of the MET-free diet administered ↔ BMI: 24.6 ± 3.vs 24.3 ± 2.9 (p = 0.12)
↔ plasma albumin: 36.0 ± 8.6 vs 36.7 ± 8.3 g/l (p = 0.76)
↓MET concentrations. Day 1: − 58.1 ± 19.1%. Day 3: − 43.3% ± 13.9%
Grade 3 neutropenia without fever (9%)
No grade 3–4 non-haematological toxicities
Thivat, 2007, France [36] Phase 1 trial with single arm assignment 6
Age NR
1 recurrent glioma, 5 metastatic melanoma
MET-free diet ranging from 1 to 4 days over 4 cycles of cystemustine chemotherapy NR NR ↓Plasma MET of 48.5 ± 4% from 23.1 ± 1.6 μg/L to 11.3 ± 0.7 μg/L (p = 0.00002)
Grade 3–4 thrombocytopenia (33%), neutropenia (33%) and leucopenia (33%)
↓ MGMT activity (fmol/mg of protein) 553 ± 90 to 413 ± 59 (p = 0.029). Mean ↓ of 36 ± 8%
No effect of duration of diet on MGMT activity after treatment
Thivat, 2009, France [37] Phase 2 trial with single arm assignment 22
Median age 62y (range 35-76y)
20 melanoma, 2 glioma
1 day MET-Free over 4 cycles cystemustine chemotherapy Patients consumed 78 ± 27% of the MET-free diet administered ↔ body weight (kg) (68.8 ± 11.5 vs. 67.8 ± 11.4, p = 0.11), plasma albumin (g/l) (from 37.8 ± 5.6 to 36.6 ± 6.8, p = 0.09) or prealbumin (g/l) (from 0.25 ± 0.1 to 0.23 ± 0.1, p = 0.32) ↓Plasma MET of 53.1 ± 21.8% after 4 h
Grade 3–4 thrombocytopenia (36%), neutropenia (27%) and leucopenia (27%)
  1. ↑ = increase
  2. ↓ = reduction
  3. ↔ = no change
  4. ≈ = approximate
  5. Where absolute figures were provided, %s have been calculated to aid comparison
  6. Abbreviations: BMI Body Mass Index, CG Control Group, DR Dietary Restriction, EV Extracellular Vesicles, FM Fat Mass, IG Intervention Group, Y/S IRS1 Insulin Receptor Substrate, LeR Leptin receptor, MET Methionine, MGMT DNA repair protein O(6)-methylguanine-DNA methyltransferase, NR Not Reported, NRI Nutrition Risk Index, Ppts Participants, RCT Randomised Controlled Trial, 3MH Urinary 3-methylhistidine